Benzodiazepines Metabolism by the Liver

Author: Bryan Hayes, PharmD
Updated: 11/13/2013

Benzodiazepine Metabolism by the Liver

Take Home Points

  • ALL benzodiazepines are metabolized by the liver. Some are just metabolized by different pathways that are less dependent on global liver function.
  • The ‘LOT’ drugs are those metabolized mostly by conjugation.

    • L – Lorazepam
    • O – Oxazepam
    • T – Temazepam
  • The ‘LOT’ drugs do not have active metabolites after hepatic conjugation, and therefore have minimally affected half-lives in patients with liver disease.

Non-LOT Benzodiazepine Medications

These benzodiazepines may have prolonged effects in patients with marked liver disease.

  • Primarily metabolized via hepatic CYP-mediated oxidation.
  • Examples: Drugs with active metabolites include -
    • Diazepam
    • Clonazepam
    • Midazolam

Some practitioners like to take advantage of the longer duration of action and active metabolites.

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  • Mihic SJ, Harris RA. Chapter 17. Hypnotics and Sedatives. In: Chabner BA, Knollmann BC, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 12nd ed. New York: McGraw-Hill; 2011. Accessed November 7, 2013.
  • Lee DC, Ferguson KL. Chapter 74. Sedative-Hypnotics. In: Lee DC, Ferguson KL, eds.Goldfrank’s Toxicologic Emergencies. 9th ed. New York: McGraw-Hill; 2011. Accessed November 7, 2013.